ethyl 6-[[(3aR,4S,6R,7S,7aR)-3-benzyl-6-(hydroxymethyl)-4-methoxy-2-oxo-4,6,7,7a-tetrahydro-3aH-pyrano[3,4-d][1,3]oxazol-7-yl]oxy]hexanoate | 1383942-03-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 6-[[(3aR,4S,6R,7S,7aR)-3-benzyl-6-(hydroxymethyl)-4-methoxy-2-oxo-4,6,7,7a-tetrahydro-3aH-pyrano[3,4-d][1,3]oxazol-7-yl]oxy]hexanoate
• CAS: 1383942-03-7
• 化学式: C₂₃H₃₃NO₈
• 分子量: 451.517
• InChiKey: REENXIBATKZEEW-FYKMYLNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 6-[[(3aR,4S,6R,7S,7aR)-3-benzyl-6-(hydroxymethyl)-4-methoxy-2-oxo-4,6,7,7a-tetrahydro-3aH-pyrano[3,4-d][1,3]oxazol-7-yl]oxy]hexanoate 在 吡啶 、 sodium azide 、 20% palladium hydroxide on charcoal 、 水 、 甲酸铵 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 N,N-diethylethanamine;6-[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(tritylamino)-2-[(tritylamino)methyl]oxan-3-yl]oxyhexanoic acid
  参考文献：
  名称：

  A Peptide Nucleic Acid–Aminosugar Conjugate Targeting Transactivation Response Element of HIV-1 RNA Genome Shows a High Bioavailability in Human Cells and Strongly Inhibits Tat-Mediated Transactivation of HIV-1 Transcription

  摘要：

  The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-I TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that the resulting PNA aminoglucosamine conjugate is stable under acidic conditions, efficiently taken up by the human cells and fairly distributed in both cytosol and nucleus without endosomal entrapment because cotreatment with endosome-disrupting agent had no effect on its cellular distribution. The conjugate displayed very high target specificity in vitro and strongly inhibited Tat mediated transactivation of HIV-1 LTR transcription in a cell culture system. The unique properties of this new class of PNA conjugate suggest it to be a potential candidate for therapeutic application.

  DOI：

  10.1021/jm300253q
• 作为产物：
  描述：

  ethyl 6-[[(3aR,4S,6R,7S,7aR)-3-benzyl-4-methoxy-2-oxo-6-(phenylmethoxymethyl)-4,6,7,7a-tetrahydro-3aH-pyrano[3,4-d][1,3]oxazol-7-yl]oxy]hexanoate 在 20% palladium hydroxide on charcoal 、 水 、 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以98%的产率得到ethyl 6-[[(3aR,4S,6R,7S,7aR)-3-benzyl-6-(hydroxymethyl)-4-methoxy-2-oxo-4,6,7,7a-tetrahydro-3aH-pyrano[3,4-d][1,3]oxazol-7-yl]oxy]hexanoate
  参考文献：
  名称：

  A Peptide Nucleic Acid–Aminosugar Conjugate Targeting Transactivation Response Element of HIV-1 RNA Genome Shows a High Bioavailability in Human Cells and Strongly Inhibits Tat-Mediated Transactivation of HIV-1 Transcription

  摘要：

  The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-I TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that the resulting PNA aminoglucosamine conjugate is stable under acidic conditions, efficiently taken up by the human cells and fairly distributed in both cytosol and nucleus without endosomal entrapment because cotreatment with endosome-disrupting agent had no effect on its cellular distribution. The conjugate displayed very high target specificity in vitro and strongly inhibited Tat mediated transactivation of HIV-1 LTR transcription in a cell culture system. The unique properties of this new class of PNA conjugate suggest it to be a potential candidate for therapeutic application.

  DOI：

  10.1021/jm300253q

文献信息

• A Peptide Nucleic Acid–Aminosugar Conjugate Targeting Transactivation Response Element of HIV-1 RNA Genome Shows a High Bioavailability in Human Cells and Strongly Inhibits Tat-Mediated Transactivation of HIV-1 Transcription
  作者：Indrajit Das、Jérôme Désiré、Dinesh Manvar、Isabelle Baussanne、Virendra N. Pandey、Jean-Luc Décout

  DOI：10.1021/jm300253q

  日期：2012.7.12

  The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-I TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that the resulting PNA aminoglucosamine conjugate is stable under acidic conditions, efficiently taken up by the human cells and fairly distributed in both cytosol and nucleus without endosomal entrapment because cotreatment with endosome-disrupting agent had no effect on its cellular distribution. The conjugate displayed very high target specificity in vitro and strongly inhibited Tat mediated transactivation of HIV-1 LTR transcription in a cell culture system. The unique properties of this new class of PNA conjugate suggest it to be a potential candidate for therapeutic application.